What is diabetes? The Diabetes Epidemic. Statistics TYPE 1. Statistics. Diabetes: Treatment and Management. Steven Ferrucci, OD, FAAO

Transcription

1 What is diabetes? Diabetes: Treatment and Management Steven Ferrucci, OD, FAAO Chief, Optometry Sepulveda VA Professor, SCCO/MBKU DM is a chronic disorder characterized by a lack of insulin or increased resistance to insulin Insulin is needed for proper uptake of glucose Clinical result is hyperglycemia retinopathy nephropathy neuropathy Statistics Approximately 9.3% of US population 29.1 Million Americans 2012: 1 out of : 1 out of 5 to 1 out of 3 Another 79 million Americans have pre-diabetes and are likely to develop diabetes if do not change habits 37% of adults age 20 or older The Diabetes Epidemic Improvements in diabetes care Pts living longer with diabetes Increased number or minority populations in US Rates of DM among minority populations are often 2-3 times greater Growth in elderly populations: 10% > 60 vs 16-20% > 80 Increasing prevalence of obesity which causes increased insulin resistance Statistics In 2007, medical expenditures for diabetes $116 billion $27 B direct care $58 B to treat diabetes related complications $31 B in excess general medical costs Medical costs 2.3 x higher in diabetic vs non-diabetic pt Actual national burden of diabetes likely exceeds $174 B when indirect costs considered Seventh leading cause of death in 2006 TYPE 1 Formerly IDDM or juvenile onset Prevalence: 0.2% 10% of all DM Most common age of onset < 30 Destruction of insulin producing B-cells in pancreas (auto-immune? viral?) Total lack of endogenous insulin Need to be on insulin to survive 1

2 TYPE 2 Formerly NIDDM or adult onset Prevalence: 8.0% 90% of all DM Most frequent age of onset > 40 Often asymptomatic Characterized by insulin resistance Strong genetic predisposition One parent, 50% likelihood Both parents, 80% Gestational Diabetes Affects 4% of all pregnancies High risk populations: Pregnant woman greater than age 25 Abnormal body weight Have first degree relatives with diabetes Hispanic, Asian, Native American, African American descent Screen in 24th to 28th week of pregnancy Gestational Diabetes Plasma glucose concentration at or above any 2 of 4 values on OGTT 1. Fasting, 95 mg/dl 2. 1 hour, 180 mg/dl 3. 2 hour, 155 mg/dl 4. 3 hour, 140 mg/dl Traditionally, treated with diet changes or insulin New studies looking at oral meds At higher risk for developing type 2 later in life 5 fold increase at 5 yrs, 9 fold after 5 years Pre-Diabetes Blood sugar levels higher than normal, but not yet high enough to be diagnosed with DM FBS: mg/dl A1c: ADA estimates 79 million Americans have prediabetes 30 minutes of exercise combined with 5-10% reduction in body weight resulted in 58% reduction in diabetes Symptoms Risk Factors Often asymptomatic, especially Type 2 Classic symptoms polydipsia polyphagia polyurea Others: weight loss, delayed wound healing, dry mouth, dry skin, recurrent infections, refractive changes Family history Specific ethnic backgrounds African Americans Native Americans Hispanic Asian American Pacific islander Sedentary Lifestyle Pertinent medical history obesity cardiovascular disease HTN High cholesterol Polycystic ovarian syndrome Psychiatric illness Gestational DM IFG/IGT 2

3 Traditional Diagnosis Fasting blood glucose > 126 mg/dl OGTT > 200 mg/dl (2 hour sample) Any random testing >200 mg/dl should be referred for further testing Random testing > 200 mg/dl with symptoms very suggestive of DM New Diagnosis Criteria Panel of experts at ADA annual meeting now recommend A1C be used for diagnosis of diabetes Glycosolated hemoglobin Tells blood sugar control over 3 months normal range 4% to 6% HgbA1c BS Level HgbA1c BS Level New Diagnosis Criteria 6.5 would be indicative of DM First major change in 30 years In adults and children, not pregnant women Advantages: Convenience: no fasting More accurate: average over 3 months Disadvantage: Cost? Recommended Criteria for Screening Asymptomatic Individuals for Type 2 DM All pts >45 yrs at 3 yr intervals Younger age or more frequently in pts who: are obese have a first-degree relative with diabetes are members of high-risk ethnic population gestational diabetes or delivered a baby > 9 lbs are hypertensive HDL < 35mg/dl or triglycerides > 250 mg/dl have impaired glucose regulation Treatment of Type 2 DM Goal: to produce desirable blood glucose levels with minimal adverse effects and maximal patient compliance Treatment begins with diet and exercise and ends with insulin Often, adequate control can be achieved with oral agents If not, insulin is utilized Sulfonylureas First FDA approved medication for type 2 DM increase insulin secretion and increase sensitivity of receptors Side effects: low incidence of side effects or drug interactions; hyperopic refractive shifts Contraindications: pregnancy, acute hyperglycemia 3

4 Sulfonylureas First generation agents (ex Diabinese) more adverse effects less expensive Second generation agents (ex Glyburide) better absorption more potent, so lower dosage more expensive First generation Acetohexamide (Dymelor) beneficial for patients with gout Chlorpropamide (Diabinese) long half-life; bad with renal disease Tolazamide (Tolinase) slowest absorption of all sulfonylureas Tolbutamide (Orinase) rapid metabolism; good with renal disease Second generation Glyburide (Diabeta,Micronase,Glynase) hyperopic shift, as much as 2 diopters Glipizide (Glucotrol) only sulfonylurea that should not be taken with food Glimepiride (Amaryl) no benefit over other agents Biguanides Metformin (glucophage): only one available in US decreases hepatic production of glucose increases peripheral glucose uptake by muscle Used as second line to sulfonylureas or in combination with them Beneficial in obese patients May improve lipid profile Metformin Side effects GI upset lactic acidosis: very serious Contraindications pregnancy alcohol abuse not with radiological contrast with caution if renal impairment Glitazones Class: Thiazolidinedines (TZD s) Rosiglitazone (Avandia) and pioglitazone (Actos) decreases insulin resistance decreases glucose production Used as first line or in combo with sulfonylureas or metformin 4

5 Glitazones Side effects HAs: most common increased fertility weight gain Contraindications pregnancy or breast feeding hepatic insufficiency Have been associated with increased rates of DME Avandia NEJM May, June 2007: Avandia (rosiglitazone, GlaxoSmithKline) has an increased cardiovascular risk Perhaps as much as 40% Estimated that as many as 6 million people have taken drug since on market 8 years ago Estimated US sales of $2.2 billion in 2006 Avandia July 2010 FDA Panel recommended keeping Avandia on market, but with warnings Did not feel the evidence presented was overwhelming Some new studies seems to indicate that risk may be almost the same with Actos FDA did put stop to trial comparing Avandia and Actos due to safety concerns Controversy continues. Avandia Avandia pulled from market in Europe Additional restrictions in US US patients can only take if unable to control blood sugar with any other drug If already on drug, must sign statement that they understand risks if wish to continue And the controversy continues. Alpha-glucosidase Inhibitors Acarbose (Precose) and Miglitol (Glyset) decreased absorption of glucose in intestines Used alone or in combo with sulfonylureas Side effects: mild GI symptoms (universal) Contraindications: inflammatory bowel disease, pregnancy Meglitinides Repaglanide (Prandin) and Nateglinide (Starlix) increase insulin secretion from pancreas Used alone or in combo with metformin Best used to control mealtime glucose Side effect HA s, GI symptoms, hypoglycemia Contraindications: liver or renal dysfunction, pregnancy 5

6 DPP-4 Inhibitors Relatively new class of medications Prevents breakdown of a naturally occurring compound in body, GLP-1, which reduces blood glucose levels in the body These allow GLP-1 to remain active in the body longer, and lower blood glucose levels ONLY when they are elevated NO risk for hypoglycemia Taken orally once a day Side effects include URI, stuffy nose, and HA Contraindications Pregnancy, renal insufficiency If taken with sulfonylureas, lower dose of sulfonylurea may be indicated Caution with Digoxin Januvia (sitagliphn) Onglyza (saxagliphn) Tradjenta (linagliphn) Nesina (alogliphn) DPP-4 Inhibitors SGLT2 Inhibitor Group of oral meds that work by Blocking 90% of glucose reabsorphon in the kidney, thereby eliminahng mg of blood glucose per day through the urine Low risk hypoglycemia Some potenhal cardiovascular concerns, deydrahon, yeast infechons Alone or with sulfonylurea or mezormin SGLT2 Inhibitor Invokana (canaglifloxin) Farxiga (dapagliflozin) GLP1- Agonists A group of medicahons administered to type 2 DM pts by injechon Increases insulin secrehon from pancreas, slows absorphon of glucose from the gut, and reduces achon of glucagon Can be used in conjunchon with sulfonylureas, TZDs or mezormin Side effects: hyoglycemia, gastrointenshnal issues, pancearhhs ContraindicaHons: Thyroid cancers, Under age 18, Stomach or inteshne issues Also reduce appehte GLP1- Agonists Bye_a (exenahde) Bydureon (exenahde XR) Victoza (liragluhde) Trulicity (dulaguhde) Tanzeum (abigluhde) 6

7 CombinaHons Pioglitazone/meZormin: Actoplus Met Glyburide/meZormin: Glucovance SitaglipHn (Januvia)/meZormin: Janumet SaxiglipHn (Onglyza)/meZormin: Kombiglyze Repaglinide(Prandin)/meZormin: Prandimet Pioglitazone/Glimepiride: Duetact AloglipHn/ mezormin: Kazano AloglipHn/ pioglitazone:oseni Pramlintide Acetate (Symlin) Synthetic analog of human amylin, a naturally occurring hormone found in the beta cells of the pancreas Used as injection in Type 1 or Type 2 DM in conjunction with mealtime insulin Insulin replaces insulin in body Used with type 2 patients who do not respond to oral agents Side effects: redness, swelling, itch at injection site risk of hypoglycemia Contraindications: hypersensitivity Insulin Long acting Insulins Glargine (Lantus) and Detemir (Levemir) Last 24 hrs with no peak Insulin Pumps Mimics natural insulin pattens More expensive than tradihonal insulin Inhaled insulin FDA approved Jan 2006 (Exubera by Pfizer) Removed from market 2010 Poor sales? Lung CA? Inhaled Insulin Afreeza by MannKind New inhaled insulin IniHally rejected by FDA in 2010 FDA cleared in June 2014 Must shll have follow up studies evaluahng risk of lung cancer In type 1 pts, must be used in conjunchon with long- achng insulin Now looks like being pulled from market ACE Inhibitors Ex lisinopril (Prinivil), benazapril (Lotensin), captopril (Capoten) etc Typically used for treatment of hypertension With diabetes: Used for kidney-protective properties to help prevent ESRD 7

8 Current recommendations for Treatment of DM Control BS levels HgbA1c < 7 Control HTN Control Cholesterol levels Total cholesterol < 200 No smoking Exercise Yearly foot exams, dental exams, and dilated retinal exams Diabetic Retinopathy Leading cause of blindness year old 8-12% of all new cases of legal blindness 50,000 Americans legally blind Early diagnosis and treatment can decrease vision loss by 50-60% Factors which influence development of DR duration of disease control of BS DuraHon of disease Type 1 Pts: ReHnopathy rare in 1 st 3-5 years Aher 10 yrs, 60% have some rehnopathy Aher 20 yrs, almost always present 50-60% PDR Type 2: 20% to 39% have rehnopathy at Hme of diagnosis Aher 15 years, 60-80% have some rehnopathy 20% chance of PDR Control of Blood Sugar DCCT Trial: 1993 Intensive blood glucose control reduced risk of developing retinopathy by 76% Slowed the progression by 54% if already had retinopathy UKPDS: 1998 for every 1% decrease in HgbA1C there is a 35% reduction in risk for retinopathy 34% reduction in retinopathy progressing with good HTN control Diabetic Retinopathy Diabetic Retinopathy Joslin Diabetes Center study Only 60% of DM s receive timely eyecare $624 million and 400,000 patients sight saved if annual eye exam and appropriate treatment March 2001: Ophthalmology 35% of DM reported no annual DFE Non-proliferative Diabetic Retinopathy (NPDR) mild moderate severe very severe Proliferative Diabetic Retinopathy (PDR) Including high-risk 8

9 Nonproliferative Diabetic Retinopathy (NPDR) Loss of retinal capillary pericytes Weakens capillary walls Causes non-perfusion in capillary beds and hypoxia Divided into mild, moderate, and severe (and very severe) Microaneurysms (ma) Dot/blot hemorrhages Mild NPDR Follow-up: 1 yr 5-10% of pts with no retinopathy will progress to retinopathy within 1 year 5-10% with mild NPDR will also progress within 1 year Moderate NPDR Marked hemorrhages/ma Cotton wool spots (CWS) Venous beading (VB) Intra-retinal microvascular abnormalities to mild degree (IRMA s) Follow Up: 6 months as many as 16% of pts with mod NPDR can progress to proliferative disease within 4 years Severe/ Very Severe NPDR Rule: Marked hemes/ma in all 4 quadrants VB in 2 or more quadrants Marked IRMA s in one quadrant Very severe: 2 of the 3 above criteria Follow-up: 3-4 months Between 10-50% of pts with this level progress to PDR within 1 year Laser is sometimes recommended Type 2 DM, associated with a 50% reduction in the rate of severe vision loss, vitrectomy and progression to high-risk PDR Rate of Progression to PDR 1 yr 5 yr Mild 5% 14% Moderate 12-26% 30-48% Severe 52% 71% Proliferative Diabetic Retinopathy (PDR) Hallmark is retinal neovascularization response to ischemia from capillary closure grow onto lattice of vitreous new vessels are fragile and easily rupture Neo divided into 2 categories NVD: on or within 2 DD of optic disc NVE: neovascularization elsewhere Follow-up: Retinal consult within 2 weeks 9

10 High Risk PDR NVD >1/4 to 1/3 disc area Any NVD with a PRH or VH Moderate to severe NVE with VH or PRH Poses very high risk of severe VH and vision loss within 2 years Follow-up: Immediate Retinal consult (24-48 hours) Clinically Significant Macular Edema(CSME) Characteristics retinal thickening at or within 500 microns (1/3 DD) of center of macula hard exudates at or within 1/3 DD if associated with thickening of adjacent retina thickening greater than 1 DD in size part of which is within 1 DD of center of macular May occur at any stage of retinopathy Treatment: retinal consult within 2 weeks CSME Other Ocular Complications Level of Retinopathy mild NPDR 3% incidence of DME moderate to severe NPDR 40% Proliferative 71% Type 2: Duration and Insulin no insulin 10 years 5% 20 years 15% on insulin 10 years 10% 20 years 30-35% Cataracts 2 to 4 times more prevalent; younger age Glaucoma 5% of DM vs 2% of general population Cranial nerve palsies III,IV, and VI VI most common; pupil sparing with III Changes in refractive error Other Ocular Complications Reduced corneal sensitivity Recurrent corneal erosions Color vision defects Small, sluggish pupils Decreased accommodation More common blepharitis Care of the diabetic patient Dilated retinal exams Timely intervention and referral to retinal specialist Patient education inform of ocular side effects retinopathy possible even with good vision report ocular symptoms associated with DM advise about organizations for support 10